Jin Zhe, Zhang Bin, Zhang Lu, Huang Wenhui, Mo Xiaokai, Chen Qiuyin, Wang Fei, Chen Zhuozhi, Li Minmin, Zhang Shuixing
The First Affiliated Hospital of Jinan University, Guangzhou, China.
The First Affiliated Hospital of Jinan University, No. 613, West Huangpu Avenue, Guangzhou, Guangdong Province 510630, PR China.
Ther Adv Med Oncol. 2020 Dec 26;12:1758835920983717. doi: 10.1177/1758835920983717. eCollection 2020.
Multiple therapies including immune-checkpoint inhibitors are emerging as effective treatment for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSSC). However, the optimal first-line and second-line treatments remains controversial.
We systematically searched databases and conducted a systematic review of phase II/III randomized controlled trials (RCTs) that compared two or more treatments for R/M HNSSC. Progression-free survival (PFS), overall survival (OS) and adverse events (AEs) ⩾3 with hazard ratios (HRs) were extracted and synthesized based on a frequentist network meta-analysis.
Twenty-six trials involving 8908 patients were included. Of first-line treatments, pembrolizumab plus cisplatin plus 5-fluorouracil is associated with significantly improved OS (P-score = 0.91) and TPEx ranked first for prolonging PFS (0.91). EXTREME plus docetaxel (0.18) ranked lowest for AEs ⩾3. Of second-line treatments, nivolumab was the highest-ranked treatment for prolonging OS (0.95), while buparlisib plus paclitaxel was the highest-ranked treatment for PFS (0.94). Subgroup analyses suggested that nivolumab was significantly associated with improvement of OS in patients with high PD-L1 expression (HR 0.55, 0.43-0.70), whereas its OS benefit is similar with conventional chemotherapy for those with low PD-L1 expression. Buparlisib plus paclitaxel showed the best OS benefit in subgroups of patients with HPV-negative status, and with oral cavity or larynx as primary tumor sites.
Pembrolizumab plus cisplatin plus 5-fluorouracil is likely to be the best first-line treatment when OS is a priority. Otherwise, TPEx should be the optimal first-line option due to its superior PFS prolongation efficacy, best safety profile, and similar OS benefit with pembrolizumab plus cisplatin plus 5-fluorouracil. Nivolumab appears to be the best second-line option with best OS prolongation efficacy and outstanding safety profile in the overall population. Future RCTs with meticulous grouping of patients and detailed reporting are urgently needed for individualized treatment.
包括免疫检查点抑制剂在内的多种疗法正在成为复发性或转移性头颈部鳞状细胞癌（R/M HNSSC）患者的有效治疗方法。然而，最佳的一线和二线治疗方案仍存在争议。
我们系统检索了数据库，并对比较两种或更多种R/M HNSSC治疗方法的II/III期随机对照试验（RCT）进行了系统评价。基于频率学派网络荟萃分析，提取并综合了无进展生存期（PFS）、总生存期（OS）以及不良事件（AE）≥3级且带有风险比（HR）的数据。
纳入了涉及8908例患者的26项试验。在一线治疗中，帕博利珠单抗联合顺铂加5-氟尿嘧啶与显著改善的OS相关（P值=0.91），且TPEx在延长PFS方面排名第一（0.91）。EXTREME联合多西他赛在AE≥3级方面排名最低（0.18）。在二线治疗中，纳武利尤单抗在延长OS方面排名最高（0.95），而布帕利西布联合紫杉醇在PFS方面排名最高（0.94）。亚组分析表明，纳武利尤单抗与高PD-L1表达患者的OS改善显著相关（HR 0.55，0.43 - 0.70），而对于低PD-L1表达患者，其OS获益与传统化疗相似。布帕利西布联合紫杉醇在HPV阴性状态、以口腔或喉为原发肿瘤部位的患者亚组中显示出最佳的OS获益。
当以OS为首要目标时，帕博利珠单抗联合顺铂加5-氟尿嘧啶可能是最佳的一线治疗方案。否则，由于TPEx具有卓越的PFS延长疗效、最佳的安全性以及与帕博利珠单抗联合顺铂加5-氟尿嘧啶相似的OS获益，它应是最佳的一线选择。纳武利尤单抗似乎是最佳的二线选择，在总体人群中具有最佳的OS延长疗效和出色的安全性。迫切需要未来进行精心分组患者并详细报告的RCT，以实现个体化治疗。
